Filiform fire needling therapy relieves T cells-mediated melanocyte apoptosis and dysfunction by inhibiting JAK/STAT3 pathway via Mfsd4a in vitiligo

We investigated the molecular mechanism of filiform fire needling therapy (FFN), an effective treatment option for vitiligo, focusing on its role in relieving depigmentation. Firstly, we validated the efficacy and safety of FFN in a study with 11 enrolled vitiligo patients. We then found that the depigmentation score was significantly improved in monobenzone-induced vitiligo mice treated with FFN. Subsequently, after being co-cultured with T-cells extracted from FFN-treated lesions, apoptosis of melanocytes was reduced and melanogenesis was enhanced. Furthermore, the gene Mfsd4a was significantly differentially expressed in melanocytes between the model group and the FFN intervention group. Further in vitro verification showed that JAK/STAT3 pathway activity was inhibited, and melanocyte activity was enhanced after knocking out Mfsd4a in co-cultured melanocytes from the monobenzone group. Moreover, interference with Mfsd4a increased MITF transcription, leading to TYR activation and promotion of melanin formation. Lastly, we found that IL-6 was involved in regulating Mfsd4a-mediated JAK/STAT3 pathway suppression, thereby regulating melanocyte survival and melanogenesis. These results demonstrate that FFN alleviates T cell-mediated melanocyte apoptosis and dysfunction by inhibiting the JAK/STAT3 pathway signaling pathway via Mfsd4a to treat vitiligo.